(adapted from the application): This application proposes the continuation of a "National Cooperative Drug Discovery Group for the Treatment of HIV infection" (NCDDG-HIV) under the direction of Dr. Jef Boeke at John Hopkins University. The overall goal of the proposed NCDDG-HIV is to develop an antiviral strategy in which virions are inactivated from within by a destructive enzyme, such as a nuclease or mutant form of a viral enzyme. The basis of this strategy, called capsid-targeted viral inactivation (CTVI), is to create and express gene fusions encoding a chimeric protein consisting of a capsid protein moiety and an antiviral protein moiety such as nuclease, and to express such fusion proteins inside virus-susceptible cells (e.g., T-cells). The continuing NCDDG-HIV would promise three Projects and one Administrative Core, and involve laboratories at John Hopkins University, the University of Alabama, and Avigen Inc., as well as several additional collaborating laboratories at various institutions.